We have further defined the involvement of activated macrophage-derived oxygen radicals in inflammation. We have found that killed cells of Actinomyces viscosus, a prevalent organism in adult dental plaque, can induce the activation of macrophages, in vivo. The activated macrophages can suppress lymphocyte proliferation, in vitro. The suppression was due to a combined effect of oxygen radicals and cyclooxygfenase products. Since granuloma formation is one form of chronic inflammation, we studied the relationship of granuloma-inducing agents to macrophage activation. Killed bacterial cells or particles of silica, bentonite or talc inhibited spleen cell activities, in vitro, and this inhibition was reversible by enhancement of antioxidant capacity of the cultures. Since another property of chronic inflammation is depression of fibroblastic repair, we examined the action of activated macrophages on fibroblast growth. Activated macrophages suppressed fibroblast proliferation by a combined effect of hydrogen peroxide and cyclooxygenase products. Further definition of the role of oxygen radicals in chronic inflammation should identify means of modulating both the tissue destructive and immune response components.